Cholinergic Flashcards
1
Q
Pilocarpine
A
Cholinergic agonist
Decreases intraocular pressure (narrow angle glaucoma)
SE: blurry vision, brow ache, miosis, SWEATING, SALIVATION
2
Q
Methacholine
A
Cholinergic agonist
Bronchoconstriction (used to diagnose asthma)
3
Q
Bethanechol
A
most GI effect; Increase peristalsis, motility, and secretions
Increase Urination
4
Q
cholinergic GI effect
A
Bethanechol (most)
Pilocarpine (not as much)
5
Q
Used for underactive bladder
A
Bethanechol
6
Q
Cause sweating
A
Pilocarpine (MOST)
Muscarine
Acrecoline (betel nuts)
7
Q
Direct cholinergic drugs
A
Ach Bethenachol Pilocarpine Cevemiline Nicotine Varenicline
8
Q
Cause significant salivation
A
PILOCARPINE
cevimeline
9
Q
What effect does IV Ach have that parasympathetics don’t?
A
Vasodilation (NO/EDGF) & Sweating
10
Q
Bethanechol
A
Quaternary – No CNS
Resistant to AchE
Selective- muscarinic receptors
Urinary/GI effects
11
Q
Tertiary Nitrogen
A
Pilocarpine- CNS to some degree
12
Q
Pilocarpine, Muscarine
A
alkaloids
Selective for muscarinic
readily absorbed orally
Pilocarpine- Tertiary N – some CNS penetration
Sweat and salivation glands sensitive to pilocarpine
13
Q
Cevimeline
A
M1 and M3, but mainly selective for M1; therefore, causes less sweating than pilocarpine
14
Q
M1
A
salivation
15
Q
M3
A
sweating, lacrimation, miosiss
16
Q
Nicotine
A
selective for nicotinic receptors; patches used to quit smoking
17
Q
Varenicline
A
partial agonist on nicotinic receptor subtype in brain
causes just enough dopamine release to relieve craving, makes smoking less pleasurable
SE: N/V, fatigue, H/a, constipation, FLATULENCE
CNS effects: sleep disturbance, vivid nightmares, pyschosis, mania, suicide
18
Q
Muscarine
A
found in some mushrooms
19
Q
Pilocarpine use
A
narrow-angle glaucoma
20
Q
Tx for postop abdominal distention or gastric atony
A
Bethanechol
21
Q
Tx for urinary retention
A
Bethanechol
22
Q
Sjogren’s tx (or dry mouth from radiation)
A
Cevimeline (1st)
Pilocarpine (less so b/c sweating side effect)
23
Q
Muscarine agonist SE
A
sweating salivation Blurry vision Abdominal cramping, N/V/D Cutaneous vasodilation Bronchoconstriction bladder tightness
24
Q
Contraindications for muscarinic agonists
A
PEPTIC ULCER
coronary insufficiency
ASTHMA/COPD
bowel obstruction
25
Muscarine poisoning from mushrooms
```
salivation, tears
N/V/D
h/a, visual disturbance
bronchospasm
bradycardia, shock
```
26
Tx muscarine poisoning
atropine (antagonist) and albuterol (reverse bronchonstriction)
27
Central effects of nicotine
low dose: alertness & attention
High dose: tremor, vomiting, increased respiration
Toxic: convulsions
28
Peripheral effects of nicotine
both sympathetic and parasympathetic
Heart (sym): increase HR, HTN; may alternate w/ vagal bradycardia
GI (parasym): N/V/D, urination
NMJ: initially causes twitches or contraction, progresses to desnsitization of NMJ and flaccid paralysis
29
Nicotine toxicity
Vomiting
CNS: convulsions, coma, respiratory arrest
NMJ block/paralysis
HTN, Cardiac arrhythmia
30
Tx for nicotine toxicity
atropine (blocks muscarinic receptors- dec. parasym effects)
Anticonvulsants
Assist respiration
31
Why can't you block nicotinic receptors in nicotine toxicity
they are all already block or desensitized
32
Cholinesterase Inhibitors
Carbamates
Edrophonium
Echothiophate
Organophosphate pesticides
33
Organophosphates
DFP, echothiopate, soman, sarin, parathion, malathion
34
Neostigmine MOA
tertiary N is attracted to negative oxygen on AchE; bind the oxygen and blocks enzymes actions; slowly hydrolyzed/released from enzyme
35
Carbamates
Neostigmine
Pyridostigmine
Pysostigmine
36
Use of cholinesterase inhibitors
reverse nerve block after surgery
37
Carbamate MOA
form covalent bond with AchE; last 30 mins-6 hours
38
Quaternary carbamates
Neostigmine and pyridostigmine -- not well absorbed orally, DO NOT cross BBB
39
Tertiary Carbamate
Physostigmine -- well absorbed orally, will get into brain
40
Edrophonium
Must be injected; VERY SHORT DURATION (5-10 minutes)
41
Echothiophate
IRREVERSIBLE bond w/ AchE
42
Echothiophate use
occasionally used for narrow angle glaucoma b/c of long-lasting effect
43
Physostigmine use
not used orally;
| topically to decrease intraocular pressure
44
Organophosphate MOA
phosphorylate AChE to form long-lasting bond; becomes irreversible w/ "aging"
45
Aging
breaking one phosphorous-oxygen bond increases the strength of bond until it becomes irreversible
46
Pralidoxime
aka 2-PAM;
| prevents aging; MUST be used with 3-4 hours
47
2-PAM MOA
strong nucleophile, which attracts the organophosphate and irreversible bind to them -- prevents attachment to AChE or pulls it off enzyme if used before aging; fatal if aging is not prevented
48
SE of 2-PAM
HTN
49
Effects of AChE inhibitors
(Parasym effects)
CNS: alertness, improve memory; convulsions, respiratory arrest w/ poisoning
Eye: miosis, near vision
GI, Bladder: stimulation, diarrhea, urination
Resp: salivation, secretion, bronchoconstriction
CV: bradycardia, dec. force of contraction, decreased CO
- little effect on BP: no cholinergic innervation
Low conc: increase muscle strength
Higher conc: twitches, fasiculations, neuromuscular blockade, paralysis
50
Neotstigmine
~4 hours
quaternary - no CNA, poorly absorbed orally, but still used
some direct NMJ effect
51
Use of neostigmine
increase bladder motility
reverse neuromuscular blockade in surgery
treat myasthenia gravis
52
Edrophonium use
diagnosis of myathenia gravis: if myathenic, muscle strength will improve for 5 min;
used to see if AChE inhibitor dose is right: edrophonium decreases strength if dose too high, increase strength if dose too low
53
Physostigmine use
glaucoma (eye drops)
| muscarinic antagonist poisoning (only systemic use b/c it is the only agonist that gets into CNS)
54
Organophosphates
Diisopropyl fluorophosphate (DFP) - prototype
Soman, Sarin, Tabun (nerve gases, fast acting)
Malathion (thiophosphate, lipid soluble -- not activated well by birds and mammals-- used to overspray for mosquito control)
Parathion-many poisonings, taken off market
55
Fast acting organophosphates
soman, sarin, tabun
56
Tx for organophosphate poisoning
Atropine-until pupils dilate
2-PAM (if w/i 3-4 hrs)
Diazepam for seizures
respiration
57
Prophylaxis (troops) for organophosphates
Pyridostigmine
58
AChE inhibitor toxicity
SLUDGE:
Salivation, lacrimation, urination, defecation, gastric distress, emesis
also: miosis, sweating, bronchoconstriction, nausea, vomiting diarrhea, bradycardia, hypotension
CNS: confusion, atazia, slurring, convulsions, coma, NMJ stimulation followed by blockade, causing paralysis
59
Antimuscarinic (anticholinergic) MOA
bind to muscarinic receptor; don't activate receptor but displace Ach or agonist from receptor
60
Prototype antimuscarinic
Atropine
61
Muscarinic antagonists
atropine- enters CNS only at very high dose
Scopolamine (more lipid soluble, into brain easily)
Tropicamide/Homatropine (eyes)
Glycopyrrolate (surgery)
Ipratropium, tiotropium (asthma, COPD)
62
Scopolamine
into brain easily (euphoria, sedation, amnesia);
| used as transdermal patch for motion sickness
63
Use of scopolamine
motion sickness
64
Effects of atropine
salivary, sweat glands, bronchioles affected at low dose
heart and eye
GI, urinary tract at high doses
65
Effects of atropine
```
DRY MOUTH!, decreased sweating
increased HR
Blurred vision, tachy, palpitation
urinary retention, hot/dry skin, fatigue
weak pulse, hallucination, delirium, coma
```
66
Drugs that block muscarinic receptors
```
older antihistamines (benedryl)
antidepressant
antipychotics
GI meds
(poisoning common)
```
67
CNS effects of antimuscarinics
atropine: little, except at toxic doses; stimulation follow by depression, can cause confusion/coma
scopolamin: drowsiness, memory loss; relieves motion sickness, dries up secretions, pre-anesthesia; toxic: hallucination, agitiation, coma
68
eye antimuscarinics
mydriasis, lens flattens; angle gets smaller (bad in narrow-angle glaucoma); photophobia; dry eyes
69
cycloplegia
loss of accommodation for near vision (inhibit ciliary muscle)
70
Use of scopolamine
pre-anesthetic, motion sickness
71
Contraindication of anticholinergics
narrow angle glaucoma
72
CV effects of anticholinergics
tachycardia (dec. vagal tone- blocks M2 receptors leading to inc. NE release); little vagal tone in babies or elderly so atropine will have little CV effect;
little blood vessel effect (no inputs) -- may block NO release;
Atropine @ high dose: vasodilation in face to decrease heat
73
Respiratory use of antimuscarinics
reverse bronchoconstriciton, cause broncodilation (useful in ACUTE asthma attacks, COPD) (ipratropium, tiotropium)
74
Respiratory antimuscarinics
tiotropium, ipratropium
75
GI antimuscarinics
Dicyclomine
| Atropine-Diphenoxylate (Lomotil)
76
Dicyclomine use
decrease motility and GI secretions (antispasmodic)
77
Atropine-diphenoxylate (lomotil) use
diarrhea
78
GU antimuscarinics
(tinkling frequently on toilets during summer)
```
Tolterodine
Fesoterodine
Oxybutynin
Trospium
Darifenacin
Solifenacin
```
79
Atropine use
decrease bradycardia
| reverse AV block
80
Glycopyrrolate use
surgery to decrease vagal tone (brady and secretions);
| decrease muscarinic side effects when neotigmine or other cholinesterase inhibitors are used to reat myathenia gravis
81
Side effects of antimuscarinics
```
dry mouth
dry eyes
tachycardia
mydriasis
decrease GI motility
Urinary retention
Hot, dry skin (high doses)
```
82
Contraindication of antimuscarinics
glaucoma
| BPH
83
Atropine overdose
dry as a bone, blind as a bat, red as a beet, mad as a hatter
tx: supportive, phystogimine (gets into CNS)
84
NMJ blockade
block nicotinic receptor on skeletal muscle:
85
Depolarizing NMJ blocker
stimulates, densensitizes, leads to paralysis (Succinylcholine)
86
Non-depolarizing NMJ Blocker
competitive antagonist for nicotinic receptor; can be overcome by increasing Ach concentration (D-Tubocurarine); highly ionized -- must be injected
87
non-depolarizing drug used in surgery
D-Tubocurarine
Rocuronium
Vecuronium
Cisatracurium
88
Reversal of non-depolarizing NMJ block
AChE inhibitor -- Neostigmine (or edrophonium)
89
non-depolarizing blocking order
Onset: 1-6 minutes
small muscles --> trunk --> respiratory last
Respiratory first to cover --> thumb last to recover
(if thumb is recovered, they know lungs have recovered so they can take off ventilator)
90
Succinylcholine facts
worst VERY FAST -- used for intubation
| Depolarizes before blocking, very brief action w/ rapid onset
91
Hydrolysis of succinylcholine
pseudocholiesterase
genetic differences in hydrolysis - expressed in terms of dibucaine number; dibucaine is a local anesthetic that causes inhibition of cholinesterase; normal dibucaine inhibition (80%), 20% means cholinesterase is abnormal and effects of succinylcholne can last hours, instead of minutes; AchE inhibitor will prolong action
92
Low dibucain (20%)
succinylcholine will last hours instead of minutes
93
Succinylcholine times
onset: 1 minutes
duration: 5-10 minutes (unless low dibucaine)
94
Side effect of succinylchline
Hyperkalemia: K+ released when nicotinic receptors stimulated; may lead to cardiac arrest - most common w/ denervated muscle or burns (nicotinic receptors upregulated)
95
Contraindications of succinylcholine
```
extensive soft tissue damage
severe burns
nontraumatic rhabdo
quadriplegia, paraplegia
muscular dystrophy
in children < 8 (unless emergency)
```
96
NMJ blocker interactions
inhaled anesthetics (halothane) - uncontrolled release of caclium from SR leading to muscle rigidity and high temperature (MALIGNANT HYPERTHERMIA)
97
Tx for malignant hyperthermia
dantrolene
98
Ganglion Blockers
Hexamethonium; mecamylamine
not used clinically
99
Effects of ganglion blockade
effects dependent on dominant tone:
Eye: cycloplegia, mydriasis
Blood vessels: dilation, orthostatic hypotension
Heart: contractility blocked, decreased vagal tone- tachycardia
GU: decreased bladder tone, retention w/ BPH, erection/ejaculation reduced
No sweating
Reflex responses to brain blocked -- no ability of ganglion to send messages to brain
100
Hexamethonium man
```
pink, pale (can't constrict veins)
warm, dry
placid, can't cry
doesn't blush or get pale
no sweat
dry mouth
far-sighted
urinary retention, impotence
constipated
```
